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Consult rounds: Hyperammonemic encephalopathy in the setting of myeloma

Can paraproteinemia cause an elevated ammonia level?

While liver disease and certain medications are known to cause
hyperammonemia, myeloma is a rare cause of hyperammonemia. One of the first
cases published on this topic was back in 2002 in NEJM.

Here are some cases published in the literature.


retrospective study shed more light
. In this study of individual patients
diagnosed with ammonia related disease from myeloma was evaluated( 27
patients), interesting findings were noted. The mean age
was 76 years with a 5:1 male-to-female ratio. All had stage III based on the
International Staging Scale (ISS). Bone marrow biopsies demonstrated 54–98%
(mean 69%) plasma cell infiltration. IgA subtype was the most common. The mean ammonia level was 113
umol/L. No intracranial processes were
detected on imaging. Three patients had improvement in mental status and
decreased ammonia levels after chemotherapy; the other three patients declined
further interventions. Inpatient mortality was over 66%. 

    The authors also did a MEDLINE
search revealing 20 articles originating from the United States and Japan
detailing a total of 32 patients who were diagnosed with myeloma induced
hyperammonemic encephalopathy. The mean age was 52 years  with an equal distribution between men and women. The average ammonia level
amongst these patients was 121 umol/L with as high as 299umol/L.  All these
patients had stage III disease by the ISS or the Durie-Salmon system. IgG was
the most common subtype at 44% (n=12), followed by IgA with 37% (n=10), light
chain multiple myeloma with 11% (n=3), and IgD with 7% (n=2). Of the 25
patients that received chemotherapy, 15 (60%) survived until discharge. The
inpatient mortality was 40% (n=10). Those patients who did not receive
chemotherapy had a lower rate of survival at 25%.

Some studies report beneficial
effects in using hemodialysis to remove excess ammonia. Several
others suggest that the initiation of aggressive chemotherapy is the most
effective measure to achieve normal ammonia levels and clinical improvement.  Mechanism of this association is still unclear. 

It is important to consider myeloma
as a cause of hyperammonemia.